rs9321939

chr6-143733635-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100164.2(PHACTR2):c.215-15350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,094 control chromosomes in the GnomAD database, including 2,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2716 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

Genes affected

PHACTR2 (HGNC:20956): (phosphatase and actin regulator 2) Predicted to enable actin binding activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in plasma membrane and platelet alpha granule membrane. Implicated in Parkinson's disease and multiple sclerosis. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR2	NM_001100164.2	c.215-15350T>C		intron_variant		ENST00000440869.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR2	ENST00000440869.7	c.215-15350T>C		intron_variant		2	NM_001100164.2	A1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25775 AN: 151976 Hom.: 2718 Cov.: 32

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25779 AN: 152094 Hom.: 2716 Cov.: 32 AF XY: 0.167 AC XY: 12441 AN XY: 74346

Gnomad4 AFR AF: 0.0498

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.0957

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.156

Alfa AF: 0.202 Hom.: 450

Bravo AF: 0.153

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	11
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9321939; hg19: chr6-144054772; COSMIC: COSV59852488;